Assessment of Bone Lesions with 18F-FDG PET Compared with 99mTc Bone Scintigraphy Leads to Clinically Relevant Differences in Metastatic Breast Cancer Management

Suzanne C. van Es; Ton Velleman; Sjoerd G. Elias; Frederike Bensch; Adrienne H. Brouwers; Andor W.J.M. Glaudemans; Thomas C. Kwee; Marleen Woltman-van Iersel; John H. Maduro; Sjoukje F. Oosting; Elisabeth G.E. de Vries; Carolina P. Schröder

doi:10.2967/jnumed.120.244640

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FIGURE 1.
Flow chart visualizing selection of patients and how they are analyzed. UMCG = University Medical Center Groningen; CAD = calcium, vitamin D.
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FIGURE 2.
Pie chart visualizing number of patients with clinically relevant difference in management recommendations after ¹⁸F-FDG PET plus ceCT (n = 16) and BS plus ceCT (n = 1).
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FIGURE 3.
Example patient with clinically relevant difference in management recommendation after ¹⁸F-FDG PET plus ceCT compared with BS plus ceCT (patient 14 of Table 3). (A) ceCT visualized 1 bone metastasis in T5 (transversal section of ceCT through T5) and 3 equivocal lesions in iliac bone (1 on left, 2 on right). (B) BS visualized no bone lesions. (C) Maximum-intensity-projection ¹⁸F-FDG PET visualized 13 bone lesions (C) (C3, C5, T5, L3, L4, sacral bone [2], left acetabulum, right costa 7, left costa 5 [2], right humerus, and sternal bone). No equivocal lesions on ceCT were detected as metastases on ¹⁸F-FDG PET.

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TABLE 1

Patient Characteristics

Parameter	Data
Breast cancer type
Invasive carcinoma^*	84 (82)
Lobular	13 (13)
Other	5 (5)
Tumor characteristics, primary
Elston grade 1	8 (8)
Elston grade 2	59 (58)
Elston grade 3	33 (32)
Elston grade unknown	2 (2)
HR-negative	17 (17)
HR-positive	85 (83)
HER2-negative	78 (76)
HER2-positive	24 (24)
Triple-negative	7 (7)
Metastasis
HR-negative	16 (16)
HR-positive	81 (79)
HER2-negative	77 (75)
HER2-positive	20 (20)
Triple-negative	7 (7)
Unknown	5 (5)
Time to tumor recurrence (mo)	77.5 (0.3–293.5)

↵* No special type; previously known as ductal.
HR = hormone receptor; HER2 = human epidermal growth factor receptor 2.
Qualitative data are numbers followed by percentages in parentheses; continuous data are median followed by range in parentheses. n = 102 patients.

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TABLE 2

Concordance of Management Recommendations by Expert Panel Based on Evaluation of Bone Lesions on BS Plus ceCT or ¹⁸F-FDG PET Plus ceCT

Recommendation	¹⁸F-FDG PET plus ceCT	BS plus ceCT	Concordant recommendation
Treatment intent
Curative	7 (6.9)	11 (10.8)	5 (4.9)
Noncurative	83 (81.4)	77 (75.5)	76 (74.5)
Unable to determine	3 (2.9)	5 (4.9)	1 (1.1)
Not evaluated^*	9 (8.8)	9 (8.8)	9 (8.8)
Systemic therapy
None	0	2 (2.0)	0
Antihormonal	57 (55.9)	53 (52.0)	51 (50)
Chemotherapy	14 (13.7)	10 (9.8)	10 (9.8)
Chemotherapy plus targeted therapy	17 (16.7)	16 (15.7)	16 (15.7)
Unable to determine	5 (4.9)	12 (11.8)	3 (2.9)
Not evaluated^*	9 (8.8)	9 (8.8)	9 (8.8)
CAD/bisphosphonate
No	15 (14.7)	27 (26.5)	14 (13.7)
Yes	77 (75.5)	62 (60.8)	62 (60.8)
Unable to determine	1 (1.0)	4 (3.9)	0
Not evaluated^*	9 (8.8)	9 (8.8)	9 (8.8)
Radiotherapy
None	62 (60.8)	56 (60.2)	39 (38.2)
Curative	10 (9.8)	6 (6.5)	2 (2.0)
Noncurative	20 (19.6)	25 (26.9)	8 (7.8)
Unable to determine	1 (1.0)	6 (6.5)	1 (1.0)
Not evaluated^*	9 (8.8)	9 (8.8)	9 (8.8)
Radiography/MRI
No	63 (61.8)	65 (63.7)	53 (52.0)
Yes	30 (29.4)	28 (27.5)	18 (17.6)
Not evaluated^*	9 (8.8)	9 (8.8)	9 (8.8)
Other imaging^†
No	92 (90.2)	66 (64.7)	39 (38.2)
Yes	1 (1.0)	27 (26.5)	1 (1.0)
Not evaluated^*	9 (8.8)	9 (8.8)	9 (8.8)

↵* For patients without bone lesions on any imaging modalities, it was assumed that management recommendations would be concordant between scenarios with ¹⁸F-FDG PET plus ceCT and BS plus ceCT and that there would be no requests for additional imaging to evaluate bone lesions, without evaluation of expert panel.
↵† Additional ¹⁸F-FDG PET in case of available BS and vice versa.
CAD = calcium, vitamin D.
Data are numbers followed by percentages in parentheses. n = 102 patients.

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TABLE 3

Predictors of Clinically Relevant Change in Management Recommendations After Evaluation of Bone Lesions by ¹⁸F-FDG PET Plus ceCT Instead of BS Plus ceCT

	Univariable analysis
Predictor	Same treatment, n = 86 (84.3%)	Difference in treatment, n = 16 (15.7%)^*	P	AUC	95% CI
Ductal histology of primary tumor (n)
No	16 (88.9%)	2 (11.1%)	0.73	0.53	0.44–0.62
Yes	70 (83.3%)	14 (16.7%)
Hormone receptor status of primary tumor (n)
Negative	12 (70.6%)	5 (29.4%)	0.14	0.59	0.46–0.71
Positive	74 (87.1%)	11 (12.9%)
HER2 status of primary tumor (n)
Negative	67 (85.9%)	11 (14.1%)	0.52	0.55	0.42–0.67
Positive	19 (79.2%)	5 (20.8%)
Grade of primary tumor (n)
Grade 1 or 2	57 (85.1%)	10 (14.9%)	0.77	0.53	0.39–0.66
Grade 3	27 (81.8%)	6 (18.2%)
Suspicion of bone metastases (n)
No	63 (85.1%)	11 (14.9%)	0.76	0.52	0.40–0.65
Yes	23 (82.1%)	5 (17.9%)
Relapse time (y)			0.70	0.53	0.37–0.69
Median	6	7
25th–75th percentiles	2%–9%	4%–10%
Bone lesions on CT (n)			0.018	0.68	0.58–0.79
Median	4	1
25th–75th percentiles	0%–20%	0%–1%

↵* For this analysis of potential predictors of management recommendations based on ¹⁸F-FDG PET, 16 patients were included. Patient with changed recommendations based on BS was not included.
AUC = area under receiver-operating-characteristic curve.